Nine-membered

A fundamental set is also called a smallest set. Usually such a smallest set is selected that it also contains the smallest rings the smallest set of smallest rings (SSSR). This makes chemical sense in indane (Figure 2-38a), for example, where only the six- and the five-membered rings are of chemical significance whereas the enveloping nine-membered ring is not. 

The cyclooctenonecarboxylate 169 undergoes smooth cycloaddition with 154 to give 170 in a good yield, but no reaction takes place with cyclooctenone (171)[111], Cyclohexenone behaves similarly. Cycloheptatrienone (172) undergoes [6-1-3] cycloaddition to form the nine-membered carbocycle 173[112],... 

Alcohol dehydrogenase-catalyzed reduction of ketones is a convenient method for the production of chiral alcohols. HLAD, the most thoroughly studied enzyme, has a broad substrate specificity and accommodates a variety of substrates (Table 11). It efficiendy reduces all simple four- to nine-membered cycHc ketones and also symmetrical and racemic cis- and trans-decalindiones (167). Asymmetric reduction of aUphatic acycHc ketones (C-4—C-10) (103,104) can be efficiendy achieved by alcohol dehydrogenase isolated from Thermoanaerohium hrockii (TBADH) (168). The enzyme is remarkably stable at temperatures up to 85°C and exhibits high tolerance toward organic solvents. Alcohol dehydrogenases from horse Hver and T. hrockii... 

Hydroxyoxaziridines like (117) undergo double ring cleavage to form, for example, a nine-membered keto lactam (81AG(E)670). 

Thomas F. McGowan, P.E., Senior Consultant, RMT/Four Nines Member, American Institute of Chemical Engineers, American Society of Mechanical Engineers, Air and Waste Management Association (Section 25, Waste Management)... 

When K.yba, Cram and coworkers attempted the synthesis of dibinaphthyl-22-crown-6 from binaphthol and diethylene glycol ditosylate. the reagent ratio was as described either by V or X (Eqs. 3.1 or 3.3). The intent was to make the 22-membered ring. Some of the 11-membered ring was isolated as well (Eq. 3.5). None was apparently observed for the benzo case because the nine-membered ring is less favorable. In short, it is not the intent of the synthesis but the reaction dynamics which determine the product. 

The course of alkylation is also influenced by the steric arrangement of the enamine. 1-Pyrrolidino-l-cycloheptene gave approximately equal quantities of the C- and N-alkylated products in dioxane, while 1-pyrroli-dino-l-cyclooctene, and 1-pyrrolidino-l-cyclononene afforded N-alkylated products exclusively under similar eonditions (29). The reason for N alkylation in the eight- and nine-membered ring compounds is to be found in the conformation of these rings, which prevents full interaction of the unshared electrons on nitrogen with the n eleetrons of the double bond. 

II. Cycles of Medium Size (Seven- to Nine-Membered Rings)... 

Reaction of perhydropyrido[l, 2-n]pyrimidine with BrCN in the presence of MgO in a 1 1 mixture of CHCI3 and MeOH at 40 °C resulted in the formation of the ten-membered 6-methoxy-3,4,7,8, 9,10-hexahydro-l,5-diazecine-l,5-(2//,6//)-dicarbonitrile. Similar reaction of perhydropyrido[l, 2-n]pyrimidin-2-one led to the nine-membered 6-methoxy-4-oxo-2,3,4,5,6,7,8,9-octahydro-l//-l,5-diazonine-l-carbonitrile (99AJC1131). 

Other advances include the construction of seven- and nine-membered rings via the analogous [4-1-3] and [6-1-3] cycloadditions with dienes and trienes respectively. Heterocycles, such as tetrahydrofurans and pyrrolidines, are accessible using carbonyl compounds and imines as substrates. The following discussion is organized around these recent discoveries. It serves to illustrate the versatility and the high degree of selectivity which are some of the distinctive features of the Pd-TMM chemistry. 

Nine-membered ring systems are potentially accessible via a TMM cycloaddition with conjugated trienes in a [6-1-3] fashion. However, tropone is the only reported system that undergoes such a reaction. Interestingly, these cydoadditions are remarkably selective in that only nine-memhered ring products are formed. 

This consists of a chairman appointed by the Secretary of State for Employment and a committee of not less than six and not more than nine members. The composition of the Commission is drawn from different groups three members may be from employers organizations and three from employees organizations. The three remaining vacancies may be filled from such organizations as local authorities and professional bodies, as the Secretary of State considers appropriate. 

With more than one heteroatom in a nine-membered fully conjugated ring system in principle there are a number of possibilities when nitrogen is present, whereas with oxygen and sulfur solely 1,4,7-triheteronine systems 1 and 3, respectively, are conceivable. Furthermore there arc mixed systems possible with different heteroatoms, i.e. 4, 5. 

Perfluoro-2-methyl-2-pentene reacted with acyclic bifunctional nucleophiles such as 2-mercaptoethanol (89NKK1772) and ethylene glycol (86JAP61200983), in the presence of a base, to give 1,4-oxathiepin and dioxepin derivatives, respectively. Eight- and nine-membered heterocycles are obtained with 1,2-bifunctional benzenes such as salicyclic acid [81JFC(18)447]. 

Scheme 16 Construction of a nine-membered cyclic ether with a (Z,Z)-1,3-diene unit by sequential RCM and silicon-assisted intramolecular cross coupling in Denmark s synthesis of brasilenyne (85) [65]...

Scheme 24 First example of RCM-based construction of a nine-membered carbocycle by altering the key disconnection in cornexistin (128)-directed work [77]...

A highlight in the application of RCM methodology in natural product synthesis is Hirama s total synthesis of ciguatoxin CTX3C (183) [90], including the more recent improved protective group strategy, as depicted in Scheme 34 [90b]. The structure of 183 spans more than 3 nm and is characterized by 12 six- to nine-membered trans-fused cyclic ethers and a spiroannulated terminal tetra-... 

Scheme 34 Formation of the central nine-membered ring and completion of the carbon skeleton in Hirama s improved total synthesis of the marine neurotoxin ciguatoxin CTX3C (183)[90b]...

Eor reviews of 76 (X = N) and other nine-membered rings containing four double bonds and a hetero atom (heteronins), see Anastassiou, A.G. Acc. Chem. Res., 1972,5, 281, Top. Nonbenzenoid Aromat. Chem., 1973,1,, Pure Appl. Chem., J975, 44, 691. For a review of heteroannulenes in general, Anastassiou, A. G. Kasmai, H.S. Adv. Heterocycl. Chem., 1978, 23, 55. 

Interestingly, 8-aminoxy acids which are homologs of y-amino acids have also been found to promote the formation of turns and helices. In apolar solvent and in the solid state, model diamides consisting of /9 -aminoxy add residues adopt a novel N-O turn stabilized by both a nine-membered H-bonded ring between C=0 and NHj+2, and a six-membered ring formed between N-O and NH +1. The X-ray crystal structure of a corresponding triamide revealed two consecutive C9 N-O turns suggesting a novel 1.79-helical fold [279]. 

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